How long does Vraylar take to work in patients with depressive episodes associated with bipolar I disorder (bipolar depression)? –
After 4-6 weeks, patients with schizophrenia treated with Vraylar 1.5 mg in clinical trials saw a significant reduction in symptoms compared with patients treated with placebo.
- 1 What to expect when first taking Vraylar?
- 2 How quickly does Vraylar work for bipolar?
- 3 Is Vraylar a strong antipsychotic?
- 4 What does Vraylar do to serotonin?
- 5 What happens if you take antipsychotics and don’t need them?
- 6 How will Vraylar make me feel?
- 7 When is Vraylar best taken?
- 8 Is Vraylar better than other antipsychotics?
- 9 Does Vraylar help with depression?
- 10 Can Vraylar treat anxiety and depression?
How fast does Vraylar work for depression?
In 6- and 8-week studies †, adults, on average, experienced improvement in their overall depression symptoms after adding VRAYLAR to their antidepressant vs an antidepressant alone.
Does cariprazine work right away?
This Vraylar (cariprazine) won’t start working right away. It might take several weeks, depending on how your body responds to this medication and what condition you’re being treated for, before you can feel noticeable improvements to your mood.
What to expect when first taking Vraylar?
IMPORTANT SAFETY INFORMATION What is the most important information I should know about VRAYLAR? Elderly people with dementia-related psychosis (having lost touch with reality due to confusion and memory loss) taking medicines like VRAYLAR are at an increased risk of death.
VRAYLAR is not approved for treating patients with dementia-related psychosis. VRAYLAR and antidepressants may increase suicidal thoughts or actions in some children and young adults especially within the first few months of treatment or when the dose is changed. Depression and other mental illnesses are the most important causes of suicidal thoughts and actions.
Patients on antidepressants and their families or caregivers should watch for new or worsening depression symptoms, especially sudden changes in mood, behaviors, thoughts, or feelings. This is very important when VRAYLAR or the antidepressant is started or when the dose is changed.
Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis that can lead to death Neuroleptic malignant syndrome (NMS): Call your healthcare provider or go to the nearest hospital emergency room right away if you have high fever, stiff muscles, confusion, increased sweating, or changes in breathing, heart rate, and blood pressure. These can be symptoms of a rare but potentially fatal side effect called NMS. VRAYLAR should be stopped if you have NMS. Uncontrolled body movements (tardive dyskinesia or TD): VRAYLAR may cause movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop taking VRAYLAR. Tardive dyskinesia may also start after you stop taking VRAYLAR. Late-occurring side effects: VRAYLAR stays in your body for a long time. Some side effects may not happen right away and can start a few weeks after starting VRAYLAR, or if your dose increases. Your healthcare provider should monitor you for side effects for several weeks after starting or increasing dose of VRAYLAR. Problems with your metabolism, such as:
High blood sugar and diabetes: Increases in blood sugar can happen in some people who take VRAYLAR. Extremely high blood sugar can lead to coma or death. Your healthcare provider should check your blood sugar before or soon after starting VRAYLAR and regularly during treatment. Tell your healthcare provider if you have symptoms such as feeling very thirsty, very hungry, or sick to your stomach, urinating more than usual, feeling weak, tired, confused, or your breath smells fruity. Increased fat levels (cholesterol and triglycerides) in your blood: Your healthcare provider should check fat levels in your blood before or soon after starting VRAYLAR and during treatment. Weight gain: Weight gain has been reported with VRAYLAR. You and your healthcare provider should check your weight before and regularly during treatment.
Low white blood cell count: Low white blood cell counts have been reported with antipsychotic drugs, including VRAYLAR. This may increase your risk of infection. Very low white blood cell counts, which can be fatal, have been reported with other antipsychotics. Your healthcare provider may do blood tests during the first few months of treatment with VRAYLAR. Decreased blood pressure (orthostatic hypotension): You may feel lightheaded or faint when you rise too quickly from a sitting or lying position. Falls: VRAYLAR may make you sleepy or dizzy, may cause a decrease in blood pressure when changing position (orthostatic hypotension), and can slow thinking and motor skills, which may lead to falls that can cause fractures or other injuries. Seizures (convulsions) Sleepiness, drowsiness, feeling tired, difficulty thinking and doing normal activities: Do NOT drive, operate machinery, or do other dangerous activities until you know how VRAYLAR affects you. VRAYLAR may make you drowsy. Increased body temperature: Do not become too hot or dehydrated during VRAYLAR treatment. Do not exercise too much. In hot weather, stay inside in a cool place if possible. Stay out of the sun. Do not wear too much clothing or heavy clothing. Drink plenty of water. Difficulty swallowing that can cause food or liquid to get into your lungs
Who should not take VRAYLAR? Do not take VRAYLAR if you are allergic to any of its ingredients. Get emergency medical help if you are having an allergic reaction (eg, rash, itching, hives, swelling of the tongue, lip, face or throat). What should I tell my healthcare provider before taking VRAYLAR? Tell your healthcare provider about any medical conditions and if you:
have or have had heart problems or a stroke have or have had low or high blood pressure have or have had diabetes or high blood sugar in you or your family have or have had high levels of total cholesterol, LDL-cholesterol, or triglycerides; or low levels of HDL-cholesterol have or have had seizures (convulsions) have or have had kidney or liver problems have or have had low white blood cell count are pregnant or plan to become pregnant. VRAYLAR may harm your unborn baby. Taking VRAYLAR during your third trimester of pregnancy may cause your baby to have abnormal muscle movements or withdrawal symptoms after birth. Talk to your healthcare provider about the risk to your unborn baby if you take VRAYLAR during pregnancy. If you become pregnant or think you are pregnant during treatment, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or http://www.womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/, are breastfeeding or plan to breastfeed. It is not known if VRAYLAR passes into breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with VRAYLAR.
Tell your healthcare provider about all medicines that you take, including prescriptions, over-the-counter medicines, vitamins, and supplements. VRAYLAR may affect the way other medicines work, and other medicines may affect how VRAYLAR works. Do not start or stop any medicines while taking VRAYLAR without talking to your healthcare provider.
What are the most common side effects of VRAYLAR? The most common side effects include difficulty moving or slow movements, tremors, uncontrolled body movements, restlessness and feeling like you need to move around, sleepiness, nausea, vomiting, indigestion, constipation, feeling tired, trouble sleeping, increased appetite, and dizziness.
These are not all the possible side effects of VRAYLAR. Please see the full Prescribing Information, including Boxed Warnings, and Medication Guide, US-VRAA-220173
How long does it take for cariprazine to start working?
Cariprazine may help control your symptoms but will not cure your condition. It may take 8 weeks or longer before you feel the full effect of cariprazine. Cariprazine is usually taken once daily with or without food.
How quickly does Vraylar work for bipolar?
Vraylar ( cariprazine ) takes time to work and patients often see a gradual reduction in symptoms over several weeks. Symptoms tend to continue to improve the longer the medication is taken. Some symptoms may not completely resolve however. Vraylar is an atypical antipsychotic used in the treatment of schizophrenia, the acute treatment of manic or mixed episodes associated with bipolar I disorder, the treatment of depressive episodes associated with bipolar I disorder, and as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD).
Why does Vraylar work so well?
Vraylar Offers an Alternative to Switching Antidepressants and Starting Over – “Unfortunately, many people with major depressive disorder — approximately 50 percent — may continue to suffer from depressive symptoms despite taking an antidepressant,” says Dr.
- Han. For these individuals, Vraylar or another add-on medication may improve symptoms and build on any progress instead of requiring the person to switch antidepressants and start over, he says.
- In the two trials used for the major depressive disorder (MDD) adjunct approval, cariprazine was deemed to improve symptoms on the basis of the average reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6 and week 8 in people with MDD treated with the drug and an antidepressant.
The scale includes questions about symptoms such as sadness, reduced sleep, reduced appetite, concentration difficulties, and suicidal thoughts. Findings from the first trial were published in March 2016 in the Journal of Clinical Psychiatry,
Is Vraylar a strong antipsychotic?
4. Bottom Line –
Vraylar is an atypical antipsychotic that is effective for the treatment of schizophrenia and bipolar disorder. Vraylar is usually well-tolerated and less likely than some other antipsychotics to cause elevations in blood sugar or total cholesterol levels, sedation, or weight gain.
Is Vraylar sedating?
Yes, sleepiness or drowsiness can be a common side effect with Vraylar in about 6% to 7% of patients compared to 4% receiving a placebo (inactive) medicine. Vraylar (cariprazine) is an oral, once daily atypical antipsychotic medicine used to treat schizophrenia, bipolar mania, bipolar depression and major depressive disorder (as an add-on medicine to antidepressant therapy) in adults.
In clinical studies of Vraylar in patients with bipolar mania, somnolence (drowsiness or sedation) was reported in 7% to 8% of Vraylar-treated patients compared to 4% of patients taking an inactive placebo. In clinical studies in patients being treated for schizophrenia, somnolence or sedation was reported in 5% to 10% of patients receiving Vraylar, and in 5% of those taking an inactive placebo. Drowsiness appears to occur more frequently with higher doses of Vraylar in patients with schizophrenia. In patients being treated with Vraylar for bipolar depression, 6% to 7% of patients reported somnolence compared to 4% of those taking a placebo.
Side effects with medications can vary between patients. Your side effects may be the same or different from other patients also taking Vraylar.
Does Vraylar actually work?
VRAYLAR works to help control the mood swings of bipolar I disorder in adults, providing full-spectrum relief for all bipolar I symptoms: bipolar I depression and acute manic or mixed episodes. Studies have shown VRAYLAR can: Improve overall depressive and manic symptoms*
What should I avoid while taking Vraylar?
Notes for Professionals: Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions. Notes for Consumers: Do not drink alcohol while taking this medication.
What does Vraylar do to serotonin?
How does Vraylar work? – Vraylar helps balance the levels of neurotransmitters in your brain. Neurotransmitters are chemicals that help your brain cells communicate with each other. The main neurotransmitters affected by Vraylar are dopamine and serotonin.
Dopamine plays a role in causing hallucinations, delusions, and thought disorders. Serotonin affects mood—low serotonin levels are associated with depression. By balancing the levels of dopamine and serotonin in the brain, Vraylar can help treat both bipolar disorder and schizophrenia. Like most antipsychotic medicines, Vraylar works gradually, so it may take some time to notice improvements in symptoms.
The most common side effects of taking Vraylar are:
- difficulty moving or slow movements
- uncontrolled body movements
- weight gain
In rare cases, antipsychotic medications like Vraylar can cause tardive dyskinesia (TD), a movement disorder that can become permanent. TD is treatable, especially if you notice it early.
What does Vraylar do to a normal person?
Generic Name: cariprazine It works by helping to restore the balance of certain natural substances in the brain. This medication can decrease hallucinations, help you to think more clearly and positively about yourself, feel less agitated, and take a more active part in everyday life.
Can you drink alcohol on cariprazine?
There are 5 alcohol/food/lifestyle interactions with Vraylar (cariprazine). Using cariprazine together with ethanol may increase side effects such as dizziness, drowsiness, confusion, and difficulty concentrating. Some people may also experience impairment in thinking, judgment, and motor coordination.
You should avoid or limit the use of alcohol while being treated with cariprazine. Do not use more than the recommended dose of cariprazine, and avoid driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until you know how the medication affects you.
Talk to your doctor if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor. Switch to professional interaction data Grapefruit juice can increase the blood levels of cariprazine.
- This may increase side effects such as extrapyramidal symptoms, cognitive and motor impairment, hyperglycemia, dyslipidemia, weight gain, orthostatic hypotension, leucopenia, neutropenia, seizures, and dysphagia.
- You should avoid the consumption of grapefruit and grapefruit juice during treatment with cariprazine.
Talk to your doctor or pharmacist if you have questions on this or other medications you are prescribed. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.
What happens if you take antipsychotics and don’t need them?
Antipsychotic drugs are harmful if you do not need them. For someone with dementia, antipsychotic drugs can make everyday activities more difficult. They also have dangerous side effects such as more anxiety, restlessness, loss of hunger or thirst, excessive sleeping and even death.
Is cariprazine a sedating?
Table 2 – Clinical Efficacy and Safety – Bipolar Disorder
|Author Year||Groups Studied And Intervention||Results And Findings||Conclusions|
|Calabrese, J. et al. (2015) 86||Phase III, double-blind trial of efficacy, safety, and tolerability of high (6–12 mg/day) and low (3–6 mg/day) doses of cariprazine in the treatment of acute manic or mixed episodes of bipolar I disorder. Efficacy parameters were change from baseline to the 3rd week in Young Mania Rating Scale (YMRS) total score and CGI-S score. NCT01058668 RGH-MD-33||The LSMD for change from baseline to the third week in the YMRS total score was statistically significant in favor of both cariprazine groups compared to placebo. On all 11 YMRS single items, both cariprazine groups demonstrated statistical significance vs. placebo. The change from baseline for both cariprazine groups was statistically significant vs. placebo regarding CGI-S scores. Common TEAEs for both cariprazine groups was akathisia; and for the 6–12 mg/day cariprazine group were tremor, nausea, and constipation.||Cariprazine was well-tolerated; however, there was a greater incidence of akathisia with cariprazine than placebo. Both high and low dose cariprazine demonstrated efficacy in treating acute manic or mixed episodes of bipolar I disorder compared to placebo.|
|Vieta, E. et al. (2015) 87||A post-hoc analysis examined the data from three similarly designed studies on the efficacy of cariprazine (3–12 mg/day) in the treatment of mania associated with bipolar I disorder. The trials included: RGH-MD-31 RGH-MD-32 RGH-MD-33||On all 11 YMRS single items, cariprazine demonstrated statistically significant superiority vs. placebo. Significantly more cariprazine patients had mild to no symptoms on 11 YMRS items vs. placebo; significantly more cariprazine patients had mild to no symptoms regarding the 4 YMRS core symptoms of speech, content, irritability, and disruptive–aggressive behavior. Significantly more cariprazine patients vs. placebo shifted from moderate/worse symptoms to mild/no symptoms on all 11, and from marked/worse symptoms to mild/no symptoms on 9 of 11 YMRS items.||Cariprazine demonstrated efficacy in treating mania associated with bipolar I disorder.|
|Sachs, G. et al. (2015) 88||Phase III trial of the efficacy of cariprazine (3–12 mg/day) in treating patients with acute manic or mixed episodes associated with bipolar I disorder. Efficacy parameters included change from baseline to the 3rd week in YMRS total score and (CGI-S) score. NCT01058096 RGH-MD-32||Cariprazine vs. placebo demonstrated a significant mean change in YMRS total score from baseline to the third week. Cariprazine vs. placebo exhibited statistically significant improvement in YMRS response, remission, mean change in CGI-S score and PANSS total score. The most common TEAEs in the cariprazine group were akathisia, tremor, extrapyramidal disorder, dyspepsia, and vomiting. Between the groups, the metabolic parameters demonstrated small and similar mean changes from baseline.||Cariprazine (3–12 mg/day) was effective in treating acute manic and mixed episodes associated with bipolar I disorder.|
|Durgam, S. et al. (2015) 89||Phase II trial on the safety, efficacy, and tolerability of cariprazine (3–12 mg/day) in the treatment of acute manic or mixed episodes associated with bipolar I disorder. NCT00488618||Cariprazine significantly decreased YMRS scores and CGI-S scores. The change for YMRS items was significant for cariprazine vs. placebo. A larger percentage of cariprazine vs. placebo-treated patients reached YMRS response and remission criteria. Akathisia, extrapyramidal disorder, headache, nausea, dyspepsia, and constipation were the most common AEs. Metabolic parameters demonstrated comparable changes except with fasting glucose in which cariprazine was associated with elevations in glucose levels vs. placebo.||Cariprazine was effective compared to placebo in treating acute manic or mixed episodes associated with bipolar I disorder.|
|Earley, W. et al. (2018) 90||Post-hoc analyses examined the data from three studies on the efficacy of cariprazine in manic and mixed episodes associated with bipolar I disorder to evaluate response and remission. The trials included: NCT00488618 NCT01058096 NCT01058668||Response rates and remission for cariprazine were greater compared to placebo.||Cariprazine improved manic symptoms. The improvement in manic symptoms did not lead to depressive symptoms.|
|McIntyre, R. et al. (2019) 91||Post-hoc analysis examined three studies regarding the efficacy of cariprazine in treating mania with mixed features associated with bipolar I disorder. The analysis looked at the cariprazine effects regarding manic and depressive symptoms. Criteria for patients with mania and mixed features: ⩾ 3 depressive symptoms (DSM-5), ⩾ 2 depressive symptoms (DS), and MADRS total score of ⩾ 10. The trials included: NCT00488618 NCT01058096 NCT01058668||The mean YMRS score for cariprazine was significant compared to placebo. YMRS response and remission criteria were met by more cariprazine-treated patients vs. placebo with the response and remission data for ⩾ 2 DS and ⩾ 10 MADRS being statistically significant. There was also. improvement in depressive symptoms vs. placebo with the data being significant for the ⩾ 10 MADRS subgroup||Manic and depressive symptoms were reduced by cariprazine in the examined subpopulations with various levels of efficacy.|
|Earley, W. et al. (2019) 92||Phase III trial assessed cariprazine in treating bipolar I depression. Efficacy parameters were changes from baseline to week 6 in MADRS score and CGI-S score. NCT02670551||Cariprazine 1.5 mg/day and 3.0 mg/day demonstrated greater efficacy by decreasing the MADRS total score vs. placebo. The data for the cariprazine groups and CGI-S scores were not statistically significant. The common TEAEs were akathisia, sedation, nausea, and dizziness. Between the groups, the metabolic and weight parameters demonstrated small and similar mean changes.||1.5 mg/day and 3.0 mg/day of cariprazine were effective in improving depressive symptoms associated with bipolar I depression.|
|Fava, M. et al. (2018) 93||Phase 2, 19 week double-blind, randomized study of adjunctive cariprazine (0.1-0.3 and 1.0-2.0 mg/day) for treatment-resistant major depressive disorder. The primary endpoint was the total score change of MADRS and the secondary endpoint was CGI-S. NCT00854100||None of the parameters met statistical significance. The 1.0–2.0 mg/day cariprazine patients had a greater mean decrease in MADRS and CGI scores.||Cariprazine was well tolerated. The mean decrease in depression symptoms with the 1.0-2.0 mg/day dose provides support for further assessment.|
|Ketter, T. et al. (2018) 94||16 week, open-label study on safety and tolerability of cariprazine (3-12 mg/day) with bipolar mania patients. Evaluations for safety included adverse events (AEs); and symptom changes included the total score change of the Young Mania Rating Scale (YMRS). ( NCT01059539 )||Common serious AEs were mania and depression.83.3% had TEAEs which included akathisia, headache, constipation, and nausea. At the sixteenth week, the mean YMRS total score decreased by –15.2.||Cariprazine was well tolerated and safe.|
|Durgam, S. et al. (2016) 53||8 week, randomized, double-blind, placebo controlled study with bipolar I patients currently experiencing a major depressive episode, 4 groups, cariprazine (0.75, 1.5, 3.0 mg/day) or placebo. The primary and secondary efficacy parameters were the score change from baseline to the sixth week on the Montgomery-Åsberg Depression Rating Scale (MADRS) and CGI-S. NCT01396447||The cariprazine 1.5mg/day group demonstrated significant improvement of total MADRS score.||Cariprazine at 1.5 mg/day showed statistically significant improvement on MADRS score and CGI-S. This dosage could possibly be an effective dose in treating bipolar I depression.|
How will Vraylar make me feel?
I wake up refreshed and feel like I’ve gotten better sleep. I concentrate at work, have a ton of energy, don’t eat all day like before and things that triggered my anger no longer affect me like before.’ ‘I started taking Vraylar 1.5 mg at bedtime almost 2 weeks ago in conjunction with my other bipolar meds.
Is Vraylar hard to get off of?
Vraylar withdrawal symptoms, like those of all antipsychotic medication withdrawals, can be difficult to manage. Without constant and careful assistance, the process can often result in repeated hospitalizations. There can be some extreme reactions and impacts on the person.
When is Vraylar best taken?
What time of day should you take Vraylar? – Even though Vraylar may be taken at any time of the day, some people may find that changing the time of day that you take Vraylar helps with certain side effects. For example, people who experience restlessness or restless legs as a side effect of Vraylar may find taking it in the morning helps.
Up to 10% of people taking Vraylar report sleepiness or drowsiness as a side effect of Vraylar, the risk of this side effect increases with higher dosages of Vraylar, and these people may prefer taking Vraylar at night. If you do experience sleepiness with Vraylar, be careful driving, operating machinery, or performing other tasks that require high levels of concentration.
Vraylar may also increase your risk of falling. Talk to your doctor if your side effects are intolerable and interfere with your day-to-day life. Alcohol may enhance or worsen the side effects of Vraylar so it is best to avoid drinking it if you have been prescribed Vraylar.
Does Vraylar stabilize mood?
– Vraylar and Seroquel are similar drugs, but they have some differences. Both are atypical (second-generation) antipsychotic drugs, meaning they work to improve your mood, thinking, and behavior. Vraylar contains the active drug cariprazine and is prescribed to treat:
manic or mixed episodes of bipolar I disorder in adults depressive episodes of bipolar I disorder in adults schizophrenia in adults major depressive disorder (MDD), often called depression, in adults*
Seroquel contains the active drug quetiapine. It’s prescribed to treat:
manic or mixed episodes of bipolar I disorder in adults† and children ages 10 and olderdepressive episodes of bipolar I disorder in adultsschizophrenia in adults and children ages 13 years and older
* For treating MDD, Vraylar is taken in combination with an antidepressant. In this situation, Vraylar is referred to as an adjunctive treatment, meaning it is not taken alone. † For treating manic or mixed episodes of bipolar I disorder, adults may take Seroquel either alone or with lithium or divalproex.
Is Vraylar better than other antipsychotics?
Which is more effective – Vraylar or Abilify? – Both Vraylar and Abilify have been shown in clinical trials to be effective for their approved uses. Ultimately, the decision of which drug to use may depend upon your condition, previous treatments, preferred formulation, side effects, cost and doctor preferences.
Abilify is approved by the FDA to treat more types of mental health disorders when compared to Vraylar. For example, Abilify may be used for Autistic disorder and for Tourette’s syndrome. Abilify comes in many different forms, such as tablets, orally disintegrating tablets, oral solution, and injections. This may be an advantage when deciding upon which medicine to use and compliance with treatment. Abilify is available in a cost-saving generic for some dosage forms like tablets and the oral solution. Abilify has been approved since 2002, which may be an advantage. Your doctor may be more familiar with its uses and side effects. Vraylar was first approved in 2015.
Advantages with Vraylar
Vraylar has a longer half-life and stays in your body longer so missing a dose or taking your dose late may not be as much of a problem as with other antipsychotics. This longer time in your body helps to stabilize blood levels with once-daily dosing. Vraylar has not been associated with as much weight gain as some other antipsychotics.
What people say about Vraylar?
Vraylar has an average rating of 5.6 out of 10 from a total of 422 reviews on Drugs.com.44% of reviewers reported a positive experience, while 39% reported a negative experience.
Does Vraylar help with depression?
VRAYLAR is a prescription medicine used in adults: along with antidepressant medicines to treat major depressive disorder (MDD) for short-term (acute) treatment of manic or mixed episodes that happen with bipolar I disorder. to treat depressive episodes that happen with bipolar I (dipolar depression)
Does Vraylar treat major depression?
VRAYLAR is a prescription medicine used along with antidepressant medicines to treat major depressive disorder (MDD) in adults.
Is Vraylar a good antidepressant?
VRAYLAR works to help control the mood swings of bipolar I disorder in adults, providing full-spectrum relief for all bipolar I symptoms: bipolar I depression and acute manic or mixed episodes. Studies have shown VRAYLAR can: Improve overall depressive and manic symptoms *
Can Vraylar treat anxiety and depression?
— Potential add-on therapy also improved most individual depressive symptoms on MADRS – by Michael DePeau-Wilson, Enterprise & Investigative Writer, MedPage Today September 20, 2022 NEW ORLEANS – Low-dose cariprazine (Vraylar) was associated with reductions in anxiety for patients with major depressive disorder (MDD), and the potential adjunctive therapy for this population also demonstrated improvements across most individual symptoms of depression, according to two post hoc analyses of a phase III trial. When combined with an antidepressant for MDD patients who had an inadequate response to monotherapy, a 1.5-mg daily dose of cariprazine showed a significantly greater reduction in anxiety compared with placebo on the Hamilton Anxiety Rating Scale (HAM-A) total score, as measured by the least squares mean difference (LSMD) from baseline. At week 6, patients on the 1.5-mg dose had a 9.1 reduction compared with a 7.8 reduction in the placebo group (LSMD -1.30, 95% CI -2.47 to -0.08, nominal P =0.037), reported Vladimir Maletic, MD, MS, of the University of South Carolina School of Medicine in Greenville, during a poster presentation at Psych Congress, No significant difference versus placebo was seen among participants in the trial who received a 3-mg daily dose. The second analysis, also presented by Maletic, showed significant improvements with cariprazine across eight of the 10 components of the Montgomery-Åsberg Depression Rating Scale (MADRS) when data for the two doses were pooled together. “In people who have not responded to their previous antidepressant treatments, if they receive cariprazine indication is that it will provide not only assistance with their depressive symptomatology but will clearly produce reduction in anxiety in patients who have mild and moderate,” he told MedPage Today, Initial findings from the phase III trial – Study 3111-301-001 – were reported earlier this year at the American Psychiatric Association annual meeting. The trial met its primary endpoint, demonstrating that adjunctive cariprazine at the lower dose led to a significant reduction in MADRS total score in these patients with MDD. Effect on Anxiety When the data for the study population was broken into groups based on baseline anxiety severity, participants with at least mild anxiety (HAM-A score >7) or at least moderate anxiety (>14) had better outcomes with the lower dose of cariprazine compared with placebo:
Mild: LSMD -1.3 (95% CI -2.52 to -0.10)Moderate: LSMD -1.6 (95% CI -2.98 to -0.23)
Participants with severe anxiety (>23) at baseline appeared to potentially derive greater benefit with either dose of cariprazine in addition to a background antidepressant, but the findings were not significant, owing to the smaller sample size, according to Maletic. “We can’t say about severe because it’s not statistically significant, but at least numerical indicators that all categories of anxious patients are likely to benefit by this combination,” he told MedPage Today, The analysis included 751 participants divided into three treatment groups – cariprazine 1.5 mg (n=250), cariprazine 3 mg (n=252), and placebo (n=249) – each combined with an antidepressant treatment. At baseline, nearly all of the participants (98.8%) had at least mild anxiety. Of those, 82.6% had at least moderate anxiety, and 34.9% had severe anxiety. Effect on MADRS Components Maletic reported that adjunctive cariprazine also produced significantly greater improvement across several MADRS scores for individual depressive symptoms compared with placebo. Significant improvements were seen versus placebo with the 1.5-mg daily dose for seven of the 10 MADRS symptoms, and pooled data for both cariprazine doses showed significant reductions in eight of the components:
Apparent sadness: LSMD -0.2 (95% CI -0.44 to -0.03, P =0.0247)
Reported sadness: LSMD -0.4 (95% CI -0.58 to -0.16, P =0.0006)
Reduced appetite: LSMD -0.3 (95% CI -0.50 to -0.10, P =0.0036)
Lassitude: LSMD -0.3 (95% CI -0.56 to -0.12, P =0.0025)
Inability to feel: LSMD -0.3 (95% CI -0.51 to -0.06, P =0.0126)
Pessimistic thoughts: LSMD -0.3 (95% CI -0.45 to -0.07, P =0.0088)
Suicidal thoughts: LSMD -0.1 (95% CI -0.20 to -0.02, P =0.0127)
Cariprazine already carries indications in schizophrenia and bipolar I disorder. Based on the findings of the current study, developer AbbVie has submitted a supplemental new drug application for an additional indication as an adjunctive treatment of MDD in patients who are receiving ongoing antidepressant therapy.
Michael DePeau-Wilson is a reporter on MedPage Today’s enterprise & investigative team. He covers psychiatry, long covid, and infectious diseases, among other relevant U.S. clinical news.
Disclosures The study was sponsored by AbbVie. Maletic reported financial relationships with AbbVie/Allergan, Acadia, Alfasigma, Alkermes, Axsome, Eisai-Purdue, Intra-Cellular, Ironshore, Janssen, Lundbeck A/S, Jazz Pharmaceuticals, Noven, Otsuka, Sage, Sunovion, Supernus, and Takeda; co-authors also reported being employees or of holding stock/options in AbbVie.